rs150959827

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_004006.3(DMD):c.2884C>G(p.Leu962Val) variant causes a missense change. The variant allele was found at a frequency of 0.000369 in 1,209,030 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 147 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00038 ( 0 hom. 141 hem. )

Consequence

DMD
NM_004006.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.32

Variant links:

Genes affected

DMD (HGNC:2928): (dystrophin) This gene spans a genomic range of greater than 2 Mb and encodes a large protein containing an N-terminal actin-binding domain and multiple spectrin repeats. The encoded protein forms a component of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extracellular matrix. Deletions, duplications, and point mutations at this gene locus may cause Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or cardiomyopathy. Alternative promoter usage and alternative splicing result in numerous distinct transcript variants and protein isoforms for this gene. [provided by RefSeq, Dec 2016]

DMD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1503506).

BP6

Variant X-32472229-G-C is Benign according to our data. Variant chrX-32472229-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 264229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3 linkuse as main transcript	c.2884C>G	p.Leu962Val	missense_variant	22/79	ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9 linkuse as main transcript	c.2884C>G	p.Leu962Val	missense_variant	22/79	1	NM_004006.3	P4

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

111679

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

33835

show subpopulations

Gnomad AFR

AF:

0.0000979

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000165

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000395

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000120

AC:

AN:

183190

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

67734

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000384

AC:

421

AN:

1097351

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

141

AN XY:

362795

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000473

Gnomad4 OTH exome

AF:

0.000456

GnomAD4 genome

AF:

0.000224

AC:

AN:

111679

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

33835

show subpopulations

Gnomad4 AFR

AF:

0.0000979

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000165

Gnomad4 NFE

AF:

0.000395

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000400

Hom.:

Bravo

AF:

0.000249

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.000743

AC:

ExAC

AF:

0.000124

AC:

EpiCase

AF:

0.000764

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	DMD: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 27, 2019	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 06, 2017

- -

Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Natera, Inc.

Aug 02, 2019

- -

Cardiovascular phenotype

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 25, 2019

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Duchenne muscular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.56

Cadd

Benign

Dann

Benign

0.29

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.83

T;.;T;T

M_CAP

Benign

0.082

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

0.74

N;N

PrimateAI

Benign

0.42

Sift4G

Benign

0.42

T;T;T;T

Polyphen

0.018

.;B;.;.

Vest4

0.30

MVP

0.53

MPC

0.12

ClinPred

0.083

GERP RS

5.2

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over